Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis

Key Points

  • Listeria monocytogenes is a food-borne pathogen that primarily afflicts immunocompromised individuals and can provoke septicaemia, meningitis and fetal infection or abortion in infected pregnant women.

  • L. monocytogenes is an excellent model for intracellular infection, as it mediates its own uptake into non-phagocytic cells, subsequently escapes from the vacuole, polymerizes actin to spread from cell to cell and secretes factors that alter transcription, post-translational modifications, innate immune signalling and cytoskeletal rearrangements.

  • L. monocytogenes can traverse three distinct epithelial barriers and competes for a niche in the dense intestinal microbiota through upregulation of metabolic pathways and the secretion of toxic bactericidal factors.

  • L. monocytogenes utilizes a plethora of complex regulation strategies such as riboregulators and small non-coding RNAs to quickly adapt to and thrive in highly divergent physiological contexts.


Listeria monocytogenes is a food-borne pathogen responsible for a disease called listeriosis, which is potentially lethal in immunocompromised individuals. This bacterium, first used as a model to study cell-mediated immunity, has emerged over the past 20 years as a paradigm in infection biology, cell biology and fundamental microbiology. In this Review, we highlight recent advances in the understanding of human listeriosis and L. monocytogenes biology. We describe unsuspected modes of hijacking host cell biology, ranging from changes in organelle morphology to direct effects on host transcription via a new class of bacterial effectors called nucleomodulins. We then discuss advances in understanding infection in vivo, including the discovery of tissue-specific virulence factors and the 'arms race' among bacteria competing for a niche in the microbiota. Finally, we describe the complexity of bacterial regulation and physiology, incorporating new insights into the mechanisms of action of a series of riboregulators that are critical for efficient metabolic regulation, antibiotic resistance and interspecies competition.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Overview of Listeria monocytogenes infection.
Figure 2: Entry of Listeria monocytogenes into cells.
Figure 3: Intestinal invasion and interaction of Listeria monocytogenes with the microbiota.
Figure 4: RNA regulation and miniproteins in Listeria monocytogenes.


  1. 1

    Murray, E. G. D., Webb, M. A. & Swann, M. B. R. A. Disease of rabbits characterised by a large mononuclear leucocytosis, caused by a hitherto undescribed bacillus Bacterium monocytogenes (n.sp.). J. Pathol. 29, 407–439 (1926).

    Google Scholar 

  2. 2

    Schlech W. F. III, Lavigne P. M., Bortolussi, R. A., Allen A. C., Haldane, E. V. et al. Epidemic listeriosis — evidence for transmission by food. N. Engl. J. Med. 308, 203–206 (1983).

    PubMed  Google Scholar 

  3. 3

    de Noordhout, C. M. et al. The global burden of listeriosis: a systematic review and meta-analysis. Lancet Infect. Dis. 14, 1073–1082 (2014).

    PubMed  PubMed Central  Google Scholar 

  4. 4

    McLauchlin, J. Human listeriosis in Britain, 1967–1985, a summary of 722 cases. 1. Listeriosis during pregnancy and in the newborn. Epidemiol. Infect. 104, 181–189 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    McLauchlin, J. Human listeriosis in Britain, 1967–1985, a summary of 722 cases. 2. Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence. Epidemiol. Infect. 104, 191–201 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6

    Weller, D., Andrus, A., Wiedmann, M. & den Bakker, H. C. Listeria booriae sp. nov. and Listeria newyorkensis sp. nov., from food processing environments in the USA. Int. J. Syst. Evol. Microbiol. 65, 286–292 (2015).

    CAS  PubMed  Google Scholar 

  7. 7

    Gandhi, M. & Chikindas, M. L. Listeria: A foodborne pathogen that knows how to survive. Int. J. Food Microbiol. 113, 1–15 (2007).

    PubMed  Google Scholar 

  8. 8

    Tasara, T. & Stephan, R. Cold stress tolerance of Listeria monocytogenes: a review of molecular adaptive mechanisms and food safety implications. J. Food Prot. 69, 1473–1484 (2006).

    CAS  PubMed  Google Scholar 

  9. 9

    de las Heras, A., Cain, R. J., Bielecka, M. K. & Vazquez-Boland, J. A. Regulation of Listeria virulence: PrfA master and commander. Curr. Opin. Microbiol. 14, 118–127 (2011).

    CAS  PubMed  Google Scholar 

  10. 10

    Cossart, P. Illuminating the landscape of host–pathogen interactions with the bacterium Listeria monocytogenes. Proc. Natl Acad. Sci. USA 108, 19484–19491 (2011).

    CAS  PubMed  Google Scholar 

  11. 11

    Bakardjiev, A. I., Theriot, J. A. & Portnoy, D. A. Listeria monocytogenes traffics from maternal organs to the placenta and back. PLoS Pathog. 2, e66 (2006).

    PubMed  PubMed Central  Google Scholar 

  12. 12

    Pizarro-Cerdá, J., Kühbacher, A. & Cossart, P. Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view. Cold Spring Harbor Persp. Med. 2, a010009 (2012).

    Google Scholar 

  13. 13

    Lambrechts, A., Gevaert, K., Cossart, P., Vandekerckhove, J. & Van Troys, M. Listeria comet tails: the actin-based motility machinery at work. Trends Cell Biol. 18, 220–227 (2008).

    CAS  PubMed  Google Scholar 

  14. 14

    Bierne, H. & Cossart, P. When bacteria target the nucleus: the emerging family of nucleomodulins. Cell. Microbiol. 14, 622–633 (2012).

    CAS  PubMed  Google Scholar 

  15. 15

    Cossart, P. & Helenius, A. Endocytosis of viruses and bacteria. Cold Spring Harbor Persp. Biol. 6, a016972 (2014).

    Google Scholar 

  16. 16

    Bierne, H., Sabet, C., Personnic, N. & Cossart, P. Internalins: a complex family of leucine-rich repeat-containing proteins in Listeria monocytogenes. Microbes Infect. 9, 1156–1166 (2007).

    CAS  PubMed  Google Scholar 

  17. 17

    Sabet, C., Lecuit, M., Cabanes, D., Cossart, P. & Bierne, H. LPXTG protein InlJ, a newly identified internalin involved in Listeria monocytogenes virulence. Infect. Immun. 73, 6912–6922 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Kühbacher, A. et al. Genome-wide siRNA screen identifies complementary signaling pathways involved in Listeria infection and reveals different actin nucleation mechanisms during Listeria cell invasion and actin comet tail formation. mBio 6, e00598-15 (2015).

    PubMed  PubMed Central  Google Scholar 

  19. 19

    Agaisse, H. et al. Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science 309, 1248–1251 (2005).

    CAS  PubMed  Google Scholar 

  20. 20

    Kirchner, M. & Higgins, D. E. Inhibition of ROCK activity allows InlF-mediated invasion and increased virulence of Listeria monocytogenes. Mol. Microbiol. 68, 749–767 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Perelman, S. S. et al. Cell-based screen identifies human interferon-stimulated regulators of Listeria monocytogenes infection. PLoS Pathog. 12, e1006102 (2016).

    PubMed  PubMed Central  Google Scholar 

  22. 22

    Xayarath, B., Alonzo, F. 3rd & Freitag, N. E. Identification of a peptide-pheromone that enhances Listeria monocytogenes escape from host cell vacuoles. PLoS Pathog. 11, e1004707 (2015).

    PubMed  PubMed Central  Google Scholar 

  23. 23

    Rabinovich, L., Sigal, N., Borovok, I., Nir-Paz, R. & Herskovits, A. A. Prophage excision activates Listeria competence genes that promote phagosomal escape and virulence. Cell 150, 792–802 (2012).

    CAS  PubMed  Google Scholar 

  24. 24

    Feiner, R. et al. A new perspective on lysogeny: prophages as active regulatory switches of bacteria. Nat. Rev. Microbiol. 13, 641–650 (2015).

    CAS  PubMed  Google Scholar 

  25. 25

    Birmingham, C. L. et al. Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature 451, 350–354 (2008).

    CAS  PubMed  Google Scholar 

  26. 26

    Lam, G. Y., Cemma, M., Muise, A. M., Higgins, D. E. & Brumell, J. H. Host and bacterial factors that regulate LC3 recruitment to Listeria monocytogenes during the early stages of macrophage infection. Autophagy 9, 985–995 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Nikitas, G. et al. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J. Exp. Med. 208, 2263–2277 (2011). This study highlights the role of L. monocytogenes transcytosis of goblet cells for intestinal epithelial barrier crossing.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Hamon, M. A., Ribet, D., Stavru, F. & Cossart, P. Listeriolysin O: the Swiss army knife of Listeria. Trends Microbiol. 20, 360–368 (2012).

    CAS  PubMed  Google Scholar 

  29. 29

    Stavru, F., Bouillaud, F., Sartori, A., Ricquier, D. & Cossart, P. Listeria monocytogenes transiently alters mitochondrial dynamics during infection. Proc. Natl Acad. Sci. USA 108, 3612–3617 (2011).

    CAS  PubMed  Google Scholar 

  30. 30

    Stavru, F., Palmer, A. E., Wang, C. X., Youle, R. J. & Cossart, P. Atypical mitochondrial fission upon bacterial infection. Proc. Natl Acad. Sci. USA 110, 16003–16008 (2013). This work reveals an atypical Drp1-independent mitochondrial fission provoked by bacterial infection that requires the ER membrane to physically constrict mitochondria and actin polymerization.

    CAS  PubMed  Google Scholar 

  31. 31

    Pillich, H., Loose, M., Zimmer, K. P. & Chakraborty, T. Activation of the unfolded protein response by Listeria monocytogenes. Cell. Microbiol. 14, 949–964 (2012).

    CAS  PubMed  Google Scholar 

  32. 32

    Kaser, A. et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134, 743–756 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

    Malet, J. K., Cossart, P. & Ribet, D. Alteration of epithelial cell lysosomal integrity induced by bacterial cholesterol-dependent cytolysins. Cell. Microbiol. 19, e12682 (2017).

    Google Scholar 

  34. 34

    Lebreton, A. et al. A bacterial protein targets the BAHD1 Chromatin complex to stimulate type III interferon response. Science 331, 1319–1321 (2011). This paper identifies LntA, the first in a class of L. monocytogenes virulence factors called nucleomodulins, which sequesters the transcriptional repressor BAHD1, thereby activating genes induced by type III interferon.

    CAS  PubMed  Google Scholar 

  35. 35

    Lebreton, A. et al. Structural basis for the inhibition of the chromatin repressor BAHD1 by the bacterial nucleomodulin LntA. mBio 5, e00775-13 (2014).

    PubMed  PubMed Central  Google Scholar 

  36. 36

    Lebreton, A. et al. A direct interaction between the bacterial nucleomodulin LntA and the chromatin repressor BAHD1 modulates interferon responses to infection. FEBS J. 281, 726–727 (2014).

    Google Scholar 

  37. 37

    Radoshevich, L. & Dussurget, O. Cytosolic innate immune sensing and signaling upon infection. Front. Microbiol. 7, 313 (2016).

    PubMed  PubMed Central  Google Scholar 

  38. 38

    Dussurget, O., Bierne, H. & Cossart, P. The bacterial pathogen Listeria monocytogenes and the interferon family: type I, type II and type III interferons. Front. Cell. Infect. Microbiol. 4, 50 (2014).

    PubMed  PubMed Central  Google Scholar 

  39. 39

    Theisen, E. & Sauer, J. D. Listeria monocytogenes and the inflammasome: from cytosolic bacteriolysis to tumor immunotherapy. Curr. Top. Microbiol. Immunol. 397, 133–160 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Hamon, M. A. et al. Histone modifications induced by a family of bacterial toxins. Proc. Natl Acad. Sci. USA 104, 13467–13472 (2007).

    CAS  PubMed  Google Scholar 

  41. 41

    Hamon, M. A. & Cossart, P. K+ efflux is required for histone H3 dephosphorylation by Listeria monocytogenes listeriolysin O and other pore-forming toxins. Infection Immun. 79, 2839–2846 (2011).

    CAS  Google Scholar 

  42. 42

    Eskandarian, H. A. et al. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341, 1238858 (2013). This study identifies a previously unknown nuclear role for SIRT2 in deacetylation of H3K18, which is downstream of InlB–Met receptor signalling and is required for effective infection.

    PubMed  Google Scholar 

  43. 43

    Samba-Louaka, A., Stavru, F. & Cossart, P. Role for telomerase in Listeria monocytogenes infection. Infect. Immun. 80, 4257–4263 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Samba-Louaka, A. et al. Listeria monocytogenes dampens the DNA damage response. PLoS Pathog. 10, e1004470 (2014).

    PubMed  PubMed Central  Google Scholar 

  45. 45

    Leitao, E. et al. Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection. Cell Cycle 13, 928–940 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Veiga, E. & Cossart, P. Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat. Cell Biol. 7, 894–900 (2005). This study demonstrates that large cargoes such as bacteria could be internalized by using the clathrin-dependent endocytic machinery.

    CAS  PubMed  Google Scholar 

  47. 47

    Bonazzi, M., Veiga, E., Pizarro-Cerda, J. & Cossart, P. Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes. Cell. Microbiol. 10, 2208–2222 (2008).

    CAS  PubMed  Google Scholar 

  48. 48

    Bonazzi, M. et al. Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization. J. Cell Biol. 195, 525–536 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Bonazzi, M. et al. A common clathrin-mediated machinery co-ordinates cell-cell adhesion and bacterial internalization. Traffic 13, 1653–1666 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Ribet, D. et al. Listeria monocytogenes impairs SUMOylation for efficient infection. Nature 464, 1192–1195 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Impens, F., Radoshevich, L., Cossart, P. & Ribet, D. Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl Acad. Sci. USA 111, 12432–12437 (2014).

    CAS  PubMed  Google Scholar 

  52. 52

    Ribet, D. et al. Promyelocytic leukemia protein (PML) controls Listeria monocytogenes infection. mBio 8, e02179-16 (2017).

    PubMed  PubMed Central  Google Scholar 

  53. 53

    Boujemaa-Paterski, R. et al. Listeria protein ActA mimics WASP family proteins: it activates filament barbed end branching by Arp2/3 complex. Biochemistry 40, 11390–11404 (2001).

    CAS  PubMed  Google Scholar 

  54. 54

    Jasnin, M. et al. Three-dimensional architecture of actin filaments in Listeria monocytogenes comet tails. Proc. Natl Acad. Sci. USA 110, 20521–20526 (2013).

    CAS  PubMed  Google Scholar 

  55. 55

    Truong, D., Copeland, J. W. & Brumell, J. H. Bacterial subversion of host cytoskeletal machinery: hijacking formins and the Arp2/3 complex. Bioessays 36, 687–696 (2014).

    CAS  PubMed  Google Scholar 

  56. 56

    Fattouh, R. et al. The diaphanous-related Formins promote protrusion formation and cell-to-cell spread of Listeria monocytogenes. J. Infect. Dis. 211, 1185–1195 (2015).

    CAS  PubMed  Google Scholar 

  57. 57

    Rigano, L. A., Dowd, G. C., Wang, Y. & Ireton, K. Listeria monocytogenes antagonizes the human GTPase Cdc42 to promote bacterial spread. Cell. Microbiol. 16, 1068–1079 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Rajabian, T. et al. The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria. Nat. Cell Biol. 11, 1212–1218 (2009). This work reveals that the L. monocytogenes virulence factor InlC alters cell rigidity in order to facilitate bacterial cell-to-cell spread.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Czuczman, M. A. et al. Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread. Nature 509, 230–234 (2014). This paper highlights the involvement of efferocytosis in the recipient cell during cell-to-cell spread.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Auerbuch, V., Brockstedt, D. G., Meyer-Morse, N., O'Riordan, M. & Portnoy, D. A. Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J. Exp. Med. 200, 527–533 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Carrero, J. A., Calderon, B. & Unanue, E. R. Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J. Exp. Med. 200, 535–540 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    O'Connell, R. M. et al. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J. Exp. Med. 200, 437–445 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Stockinger, S. et al. IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism. J. Immunol. 173, 7416–7425 (2004).

    CAS  PubMed  Google Scholar 

  64. 64

    Osborne, S. E. et al. Type I interferon promotes cell-to-cell spread of Listeria monocytogenes. Cell. Microbiol. 19, e12660 (2017).

    Google Scholar 

  65. 65

    Gutierrez, M. G. et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753–766 (2004).

    CAS  Google Scholar 

  66. 66

    Yoshikawa, Y. et al. Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat. Cell Biol. 11, 1233–1240 (2009). This paper identifies the importance of ActA-mediated autophagy evasion during L. monocytogenes infection.

    CAS  PubMed  Google Scholar 

  67. 67

    Mostowy, S. et al. p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways. J. Biol. Chem. 286, 26987–26995 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Mitchell, G. et al. Avoidance of autophagy mediated by PlcA or ActA is required for Listeria monocytogenes growth in macrophages. Infect. Immun. 83, 2175–2184 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Lecuit, M. et al. A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes. EMBO J. 18, 3956–3963 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Lecuit, M. et al. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science 292, 1722–1725 (2001).

    CAS  PubMed  Google Scholar 

  71. 71

    Pentecost, M., Kumaran, J., Ghosh, P. & Amieva, M. R. Listeria monocytogenes Internalin B activates junctional endocytosis to accelerate intestinal invasion. PLoS Pathog. 6, e1000900 (2010).

    PubMed  PubMed Central  Google Scholar 

  72. 72

    Gessain, G. et al. PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes. J. Exp. Med. 212, 165–183 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Khelef, N., Lecuit, M., Bierne, H. & Cossart, P. Species specificity of the Listeria monocytogenes InlB protein. Cell. Microbiol. 8, 457–470 (2006).

    CAS  PubMed  Google Scholar 

  74. 74

    Wollert, T., Heinz, D. W. & Schubert, W. D. Thermodynamically reengineering the listerial invasion complex InlA/E-cadherin. Proc. Natl Acad. Sci. USA 104, 13960–13965 (2007).

    CAS  PubMed  Google Scholar 

  75. 75

    Wollert, T. et al. Extending the host range of Listeria monocytogenes by rational protein design. Cell 129, 891–902 (2007).

    CAS  PubMed  Google Scholar 

  76. 76

    Tsai, Y. H., Disson, O., Bierne, H. & Lecuit, M. Murinization of Internalin extends its receptor repertoire, altering Listeria monocytogenes cell tropism and host responses. PLoS Pathog. 9, e1003381 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

    Jones, G. S. et al. Intracellular Listeria monocytogenes comprises a minimal but vital fraction of the intestinal burden following foodborne infection. Infect. Immun. 83, 3146–3156 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Jones, G. S. & D'Orazio, S. E. Monocytes are the predominant cell type associated with Listeria monocytogenes in the gut, but they do not serve as an intracellular growth niche. J. Immunol. 198, 2796–2804 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Bleriot, C. et al. Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection. Immunity 42, 145–158 (2015).

    CAS  PubMed  Google Scholar 

  80. 80

    Charlier, C. et al. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect. Dis. 17, 510–519 (2017).

    PubMed  Google Scholar 

  81. 81

    Bakardjiev, A. I., Stacy, B. A. & Portnoy, D. A. Growth of Listeria monocytogenes in the guinea pig placenta and role of cell-to-cell spread in fetal infection. J. Infect. Dis. 191, 1889–1897 (2005).

    PubMed  Google Scholar 

  82. 82

    Disson, O. et al. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature 455, 1114–1118 (2008). This study identifies key determinants required to cross the placental barrier.

    CAS  PubMed  Google Scholar 

  83. 83

    Lecuit, M. et al. Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: role of internalin interaction with trophoblast E-cadherin. Proc. Natl Acad. Sci. USA 101, 6152–6157 (2004).

    CAS  PubMed  Google Scholar 

  84. 84

    Zeldovich, V. B., Robbins, J. R., Kapidzic, M., Lauer, P. & Bakardjiev, A. I. Invasive extravillous trophoblasts restrict intracellular growth and spread of Listeria monocytogenes. PLoS Pathog. 7, e1002005 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Zeldovich, V. B. et al. Placental syncytium forms a biophysical barrier against pathogen invasion. PLoS Pathog. 9, e1003821 (2013).

    PubMed  PubMed Central  Google Scholar 

  86. 86

    Faralla, C. et al. InlP, a new virulence factor with strong placental tropism. Infect. Immun. 84, 3584–3596 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Rolhion, N. & Chassaing, B. When pathogenic bacteria meet the intestinal microbiota. Philos. Trans. R. Soc. Lond. B Biol. Sci. 371, 20150504 (2016).

    PubMed  PubMed Central  Google Scholar 

  88. 88

    Archambaud, C. et al. Impact of lactobacilli on orally acquired listeriosis. Proc. Natl Acad. Sci. USA 109, 16684–16689 (2012).

    CAS  PubMed  Google Scholar 

  89. 89

    Archambaud, C. et al. The intestinal microbiota interferes with the microRNA response upon oral Listeria infection. mBio 4, e00707-13 (2013).

    PubMed  PubMed Central  Google Scholar 

  90. 90

    Becattini, S. et al. Commensal microbes provide first line defense against Listeria monocytogenes infection. J. Exp. Med. 214, 1973–1989 (2017). This study dissects the relative contributions of the microbiota and the immune response in listeriosis and identifies four strains of bacteria that have antibacterial properties against L. monocytogenes.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91

    Becavin, C. et al. Comparison of widely used Listeria monocytogenes strains EGD, 10403S, and EGD-e highlights genomic variations underlying differences in pathogenicity. mBio 5, e00969-14 (2014).

    PubMed  PubMed Central  Google Scholar 

  92. 92

    Cotter, P. D. et al. Listeriolysin S, a novel peptide haemolysin associated with a subset of lineage I Listeria monocytogenes. PLoS Pathog. 4, e1000144 (2008).

    PubMed  PubMed Central  Google Scholar 

  93. 93

    Quereda, J. J. et al. Bacteriocin from epidemic Listeria strains alters the host intestinal microbiota to favor infection. Proc. Natl Acad. Sci. USA 113, 5706–5711 (2016). This study identifies the first bacteriocin-like virulence factor in L. monocytogenes.

    CAS  PubMed  Google Scholar 

  94. 94

    Dussurget, O. et al. Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor involved in the intestinal and hepatic phases of listeriosis. Mol. Microbiol. 45, 1095–1106 (2002).

    CAS  PubMed  Google Scholar 

  95. 95

    Begley, M., Sleator, R. D., Gahan, C. G. & Hill, C. Contribution of three bile-associated loci, bsh, pva, and btlB, to gastrointestinal persistence and bile tolerance of Listeria monocytogenes. Infect. Immun. 73, 894–904 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96

    Dowd, G. C., Joyce, S. A., Hill, C. & Gahan, C. G. Investigation of the mechanisms by which Listeria monocytogenes grows in porcine gallbladder bile. Infect. Immun. 79, 369–379 (2011).

    CAS  PubMed  Google Scholar 

  97. 97

    Toledo-Arana, A. et al. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459, 950–956 (2009).

    CAS  PubMed  Google Scholar 

  98. 98

    Mraheil, M. A. et al. The intracellular sRNA transcriptome of Listeria monocytogenes during growth in macrophages. Nucleic Acids Res. 39, 4235–4248 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99

    Wurtzel, O. et al. Comparative transcriptomics of pathogenic and non-pathogenic Listeria species. Mol. Syst. Biol. 8, 583 (2012).

    PubMed  PubMed Central  Google Scholar 

  100. 100

    Dar, D. et al. Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria. Science 352, aad9822 (2016). This fascinating paper identifies new L. monocytogenes riboregulators, one of which is critical for antibiotic resistance.

    PubMed  PubMed Central  Google Scholar 

  101. 101

    Lebreton, A. & Cossart, P. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression. RNA Biol. 14, 460–470 (2016).

    PubMed  PubMed Central  Google Scholar 

  102. 102

    Reniere, M. L. et al. Glutathione activates virulence gene expression of an intracellular pathogen. Nature 517, 170–173 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Hall, M. et al. Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria. Proc. Natl Acad. Sci. USA 113, 14733–14738 (2016).

    CAS  PubMed  Google Scholar 

  104. 104

    Mandin, P. et al. VirR, a response regulator critical for Listeria monocytogenes virulence. Mol. Microbiol. 57, 1367–1380 (2005).

    CAS  PubMed  Google Scholar 

  105. 105

    Kang, J., Wiedmann, M., Boor, K. J. & Bergholz, T. M. VirR-mediated resistance of Listeria monocytogenes against food antimicrobials and cross-protection induced by exposure to organic acid salts. Appl. Environ. Microbiol. 81, 4553–4562 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106

    Abachin, E. et al. Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol. Microbiol. 43, 1–14 (2002).

    CAS  PubMed  Google Scholar 

  107. 107

    Thedieck, K. et al. The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes. Mol. Microbiol. 62, 1325–1339 (2006).

    CAS  PubMed  Google Scholar 

  108. 108

    Behrens, S. et al. Ultra deep sequencing of Listeria monocytogenes sRNA transcriptome revealed new antisense RNAs. PloS ONE 9, e83979 (2014).

    PubMed  PubMed Central  Google Scholar 

  109. 109

    Burke, T. P. et al. Listeria monocytogenes is resistant to lysozyme through the regulation, not the acquisition, of cell wall-modifying enzymes. J. Bacteriol. 196, 3756–3767 (2014).

    PubMed  PubMed Central  Google Scholar 

  110. 110

    Boneca, I. G. et al. A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system. Proc. Natl Acad. Sci. USA 104, 997–1002 (2007).

    CAS  PubMed  Google Scholar 

  111. 111

    Burke, T. P. & Portnoy, D. A. SpoVG is a conserved RNA-binding protein that regulates Listeria monocytogenes lysozyme resistance, virulence, and swarming motility. mBio 7, e00240-16 (2016).

    PubMed  PubMed Central  Google Scholar 

  112. 112

    Quereda, J. J., Ortega, A. D., Pucciarelli, M. G. & Garcia-del Portillo, F. The Listeria small RNA Rli27 regulates a cell wall protein inside eukaryotic cells by targeting a long 5′-UTR variant. PLoS Genet. 10, e1004765 (2014).

    PubMed  PubMed Central  Google Scholar 

  113. 113

    Mellin, J. R. et al. A riboswitch-regulated antisense RNA in Listeria monocytogenes. Proc. Natl Acad. Sci. USA 110, 13132–13137 (2013).

    CAS  PubMed  Google Scholar 

  114. 114

    Mellin, J. R. et al. Sequestration of a two-component response regulator by a riboswitch-regulated noncoding RNA. Science 345, 940–943 (2014). This study identifies a two-component system that can be sequestered by a riboswitch-regulated RNA in L. monocytogenes.

    CAS  PubMed  Google Scholar 

  115. 115

    Aubry, C. et al. OatA, a peptidoglycan O-acetyltransferase involved in Listeria monocytogenes immune escape, is critical for virulence. J. Infect. Dis. 204, 731–740 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116

    Pensinger, D. A. et al. The Listeria monocytogenes PASTA kinase PrkA and its substrate YvcK are required for cell wall homeostasis, metabolism, and virulence. PLoS Pathog. 12, e1006001 (2016).

    PubMed  PubMed Central  Google Scholar 

  117. 117

    Marles-Wright, J. et al. Molecular architecture of the “stressosome,” a signal integration and transduction hub. Science 322, 92–96 (2008).

    CAS  PubMed  Google Scholar 

  118. 118

    Impens, F. et al. N-terminomics identifies Prli42 as a membrane miniprotein conserved in Firmicutes and critical for stressosome activation in Listeria monocytogenes. Nat. Microbiol. 2, 17005 (2017). This study maps the translational landscape of L. monocytogenes through a proteomics approach, thus identifying a small protein that interacts with the stressosome and affects stress signalling.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. 119

    Orsi, R. H. & Wiedmann, M. Characteristics and distribution of Listeria spp., including Listeria species newly described since 2009. Appl. Microbiol. Biotechnol. 100, 5273–5287 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120

    Maury, M. M. et al. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. Nat. Genet. 48, 308–313 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. 121

    Moura, A. et al. Whole genome-based population biology and epidemiological surveillance of Listeria monocytogenes. Nat. Microbiol. 2, 16185 (2016).

    CAS  PubMed  Google Scholar 

  122. 122

    Ragon, M. et al. A new perspective on Listeria monocytogenes evolution. PLoS Pathog. 4, e1000146 (2008).

    PubMed  PubMed Central  Google Scholar 

  123. 123

    Abdullah, Z. et al. RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids. EMBO J. 31, 4153–4164 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124

    Hagmann, C. A. et al. RIG-I detects triphosphorylated RNA of Listeria monocytogenes during Infection in non-immune cells. PloS ONE 8, e62872 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. 125

    Radoshevich, L. et al. ISG15 counteracts Listeria monocytogenes infection. eLife 4, e06848 (2015). This paper reveals an early interferon-independent induction of ISG15 in non-phagocytic cells as well as an anti-listerial function of ISGylation, which was previously thought to be primarily antiviral.

    PubMed Central  Google Scholar 

  126. 126

    Woodward, J. J., Iavarone, A. T. & Portnoy, D. A. c-Di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328, 1703–1705 (2010). This seminal paper discovers that a bacterial cyclic dinucleotide can directly activate STING to upregulate type I interferon.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. 127

    Archer, K. A., Durack, J. & Portnoy, D. A. STING-dependent type I IFN production inhibits cell-mediated immunity to Listeria monocytogenes. PLoS Pathog. 10, e1003861 (2014). This paper explores the idea that L. monocytogenes secretes cyclic di-AMP because early activation of innate immune signalling has a deleterious effect on T cell-mediated immunity following subsequent exposure.

    PubMed  PubMed Central  Google Scholar 

  128. 128

    McFarland, A. P. et al. Sensing of bacterial cyclic dinucleotides by the oxidoreductase RECON promotes NF-κB activation and shapes a proinflammatory antibacterial state. Immunity 46, 433–445 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129

    Ribet, D. & Cossart, P. How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect. 17, 173–183 (2015).

    CAS  PubMed  Google Scholar 

  130. 130

    Quereda, J. J. & Cossart, P. Regulating bacterial virulence with RNA. Annu. Rev. Microbiol. 71, 263–280 (2017).

    CAS  PubMed  Google Scholar 

Download references


The authors apologize to those colleagues whose work could not be included owing to space constraints. The authors gratefully acknowledge financial support from the European Research Area Network (ERA-NET) Infect-ERA BACVIRISG15 and PROANTILIS, the European Research Council (ERC) Advanced Grant BacCellEpi (670823), Agence Nationale de la Recherche (ANR) BACNET (10-BINF-02-01), ANR Investissement d'Avenir Programme (10-LABX-62-IBEID), Human Frontier Science Program (HFSP; RGP001/2013), the Balzan Foundation, the Pasteur-Weizmann Council and the Fondation le Roch les Mousquetaires. The authors thank D. Ribet, J.J. Quereda, S. Brisse and M. Lecuit for allowing us to adapt their figures. The authors thank H. Bierne, J. Pizarro-Cérda and O. Dussurget for helpful discussions. L.R. is supported by an HFSP long-term fellowship. P.C. is a senior international research scholar of the Howard Hughes Medical Institute, USA.

Author information




L.R. and P.C. researched the data for the article, wrote the article, provided a substantial contribution to discussions of the content and reviewed and edited the manuscript before submission.

Corresponding authors

Correspondence to Lilliana Radoshevich or Pascale Cossart.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

PowerPoint slides


Actin nucleation

The assembly of monomeric actin into filaments by actin nucleators, which can result in branched or linear actin filaments depending on the actin nucleator.

Actin-based motility

Listeria monocytogenes-mediated motility co-opts cellular actin nucleators to form bundles of actin that propel the bacterium within the cell and allow it to spread from one cell to another.

Receptor-mediated endocytosis

Cellular uptake of host surface receptors to regulate growth factor signalling or receptor turnover; the process requires monoubiquitylation of the receptor, clathrin and actin.


A Listeria monocytogenes protein characterized by leucine-rich repeat domains that can be anchored to the bacterial cell wall by a sorting motif or secreted.

Vacuolar rupture

Vacuolar damage (or phagosomal damage in phagocytic cells) by bacterial virulence factors that allow bacterial escape into the cytosol.

Phage excision

The active process of removal of DNA from a lysogenic (non-lytic) bacteriophage that was previously integrated into the bacterial genome.

LC3-mediated phagocytosis

Phagocytosis in which the autophagy microtubule-associated protein light-chain 3 (LC3) is conjugated to the lipid phosphatidylethanolamine on the inside of the plasma membrane.

Mitochondrial fission

Mitochondrial division mediated by dedicated cellular factors called dynamin-related protein 1 (DRP1 and mitochondrial fission factor (Mff).

Unfolded protein response

(UPR.) When the protein folding demand of the endoplasmic reticulum (ER) exceeds its capacity, this response upregulates chaperones, blocks translation into the ER and increases ER folding capacity.


A class of proteases that degrade other proteins and are typically activated by the acidic conditions in the lysosome.


A class of bacterial virulence factors that are expressed in the cytoplasm and travel to the nucleus where they can affect host transcription.

Bromo adjacent homology domain-containing 1 protein

(BAHD1). A protein that is part of a transcriptional repression complex that affects the expression of interferon-stimulated genes following Listeria monocytogenes infection.


A protein that is important in endocytosis and exocytosis and has heavy chain variants and light chain variants that form a polyhedral lattice on the surface of vesicles.


The process by which a small ubiquitin-like modifier covalently binds to its substrates. This typically leads to changes in localization or sequestration of transcription factors resulting in transcriptional repression.


A family of proteins that polymerize actin; each formin can have distinct actin-nucleating properties depending on the family.

Diaphanous formins

A subset of formins that have an autoinhibitory domain that is released by binding to GTPases.


The process for phagocytosing dead or dying cells that is initiated by the recognition of phosphatidylserine lipids on the cell surface (lipids normally present on the internal side of the plasma membrane).


A catabolic process that can nonspecifically or selectively capture cytosolic contents, organelles or invading pathogens and target them for degradation in the lysosome.


A programmed cell death process, distinct from apoptosis, which generates inflammatory signals and typically occurs during infection.


Cells that will form the placenta, which are derived from fetal tissue and form the external layer of the developing blastocyst in the context of pregnancy.


A condition in which the precise contents of the microbiota (bacteria and other microorganisms) of an animal are known; can refer to zero bacteria (germ-free) or a known subset of bacteria.

Immune priming

Transcriptional activation of innate defence pathways or immune memory pathways that leads to a subsequent downstream immune response that is more pronounced than the initial naive immune response.

ANTAR element

An RNA-binding domain called AmiR and NasR transcriptional anti-terminator regulator (ANTAR).

Attenuation-like mechanism

A mechanism of transcriptional control in bacteria and archaea that incorporates a terminator sequence into the 5′ mRNA leader that can stall the ribosome (resulting in aborted translation) or allow readthrough depending on metabolic conditions.

Ribosomal stalling

An event that occurs when the ribosome slows during translation, often owing to a specific secondary structure in the mRNA, resulting in aborted translation or temporary ribosomal pausing.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Radoshevich, L., Cossart, P. Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis. Nat Rev Microbiol 16, 32–46 (2018).

Download citation

Further reading


Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing